Spironolactone prevents aldosterone induced increased duration of atrial fibrillation in rat

Cell Physiol Biochem. 2012;29(5-6):833-40. doi: 10.1159/000178483. Epub 2012 May 11.

Abstract

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. The Renin-Angiotensin-Aldosterone-System plays a major role for the atrial structural and electrical remodelling. Recently elevated aldosterone levels have been suggested to increase the risk for the development of AF.

Methods: Rats were treated with aldosterone by means of an osmotic minipump (0.5μg/h) over a period of 4 weeks. AF was induced by transesophageal burst pacing. Action potentials (AP) were recorded from left atrial preparations with microelectrodes. Atrial collagen was quantified by histological studies.

Results: Aldosterone treatment resulted in hypertrophy as indicated by an increased ratio of heart weight/tibia length and doubled the time until the AF converted spontaneously into sinus rhythm (85.8±13.4 s vs. 38.3±6.9 s, p<0.01). This was associated with a significant shortening of the AP (APD90 26.2±1.1 vs. 31.2±1.9, p<0.05) and an increased protein expression of Kir2.1 and Kv1.5. Atrial collagen deposition was significantly greater in aldosterone-treated rats. The alterations could be prevented by additional application spironolactone.

Conclusions: The results of the present study suggest that in addition to the structural remodelling aldosterone also promotes AF by altering repolarising potassium currents leading to action potential shortening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Aldosterone / adverse effects*
  • Aldosterone / pharmacology
  • Animals
  • Atrial Fibrillation / physiopathology
  • Atrial Fibrillation / prevention & control*
  • Blood Pressure
  • Blotting, Western
  • Male
  • Rats
  • Rats, Wistar
  • Spironolactone / pharmacology*

Substances

  • Spironolactone
  • Aldosterone